Showing papers by "Guillermo Torre-Amione published in 1995"

Tumor necrosis factor-alpha gene and protein expression in adult feline myocardium after endotoxin administration.

Abstract: TNF alpha mRNA and protein biosynthesis were examined in the adult feline heart after stimulation with endotoxin. When freshly isolated hearts were stimulated with endotoxin in vitro, de novo TNF alpha mRNA expression occurred within 30 min, and TNF alpha protein production was detected within 60-75 min; however, TNF alpha mRNA and protein production were not detected in diluent-treated hearts. Immunohistochemical studies localized TNF alpha to endothelial cells, smooth muscle cells, and cardiac myocytes in the endotoxin-treated hearts, whereas TNF alpha immunostaining was absent in the diluent-treated hearts. To determine whether the cardiac myocyte was a source for TNF alpha production, two studies were performed. First, in situ hybridization studies, using highly specific biotinylated probes, demonstrated TNF alpha mRNA in cardiac myocytes from endotoxin-stimulated hearts; in contrast, TNF alpha mRNA was not expressed in myocytes from diluent-treated hearts. Second, TNF alpha protein production was observed when cultured cardiac myocytes were stimulated with endotoxin, whereas TNF alpha protein production was not detected in the diluent-treated cells. The functional significance of the intramyocardial production of TNF alpha was determined by examining cell motion in isolated cardiac myocytes treated with superfusates from endotoxin- and diluent-stimulated hearts. These studies showed that cell motion was depressed in myocytes treated with superfusates from the endotoxin-treated hearts, but was normal with the superfusates from the diluent-treated hearts; moreover, the negative inotropic effects of the superfusates from the endotoxin-treated hearts could be abrogated completely by pretreatment with an anti-TNF alpha antibody. Finally, endotoxin stimulation was also shown to result in the intramyocardial production of TNF alpha mRNA and protein in vivo. Thus, this study shows for the first time that the adult mammalian myocardium synthesizes biologically active TNF alpha.

Tumor necrosis factor‐α and the failing human heart–TNFα and heart failure

Abstract: Tumor necrosis factor-alpha (TNF alpha) is a proinflammatory cytokine with negative inotropic effects. Recently, elevated levels of TNF alpha have been identified in patients with advanced heart failure. Although the clinical significance of this finding is unclear at present, there is increasing evidence that this cytokine may play a primary pathophysiologic role in the development and pathogenesis of heart failure in humans. Indeed, many of the clinical hallmarks of heart failure, including left ventricular dysfunction, cardiomyopathy, and pulmonary edema can be explained by the known biological effects of TNF alpha in humans. The present review will summarize recent evidence with regard to the biological role for TNF alpha in the adult mammalian heart, as well as summarize the increasing body of clinical information that implicates this cytokine in the pathophysiology of heart failure.

Tumor necrosis factor-α and failing human heart

Abstract: Tumor necrosis factor-alpha (TNFα) is a proinflammatory cytokine with negative inotropic effects. Recently, elevated levels of TNFα have been identified in patients with advanced heart failure. Although the clinical significance of this finding is unclear at present, there is increasing evidence that this cytokine may play a primary pathophysiologic role in the development and pathogenesis of heart failure in humans. Indeed, many of the clinical hallmarks of heart failure, including left ventricular dysfunction, cardiomyopathy, and pulmonary edema can be explained by the known biological effects of TNFα in humans. The present review will summarize recent evidence with regard to the biological role for TNFα in the adult mammalian heart, as well as summarize the increasing body of clinical information that implicates this cytokine in the pathophysiology of heart failure.